Rural barriers to early lung cancer detection: Exploring access to lung cancer screening programs in New Hampshire and Vermont

BackgroundRural populations face many health disadvantages compared to urban areas. There is a critical need to better understand the current lung cancer screening landscape in these communities to identify targeted areas to improve the impact of this proven tool.MethodsData from the County Health Rankings of New Hampshire and Vermont was reviewed for population density, distribution of adult smokers, and level of education compared to the distribution of Lung Cancer Screening Facilities throughout these two states.ResultsScreening programs in southern counties of Vermont with lower levels of education have decreased access. In New Hampshire, there are no programs within 30 miles of the areas with the largest distribution of smokers, and decreased access in some areas with the lowest levels of education.ConclusionsImproving equitable access to high-quality screening services in rural regions and the creation of targeted interventions to address decreased access in areas of high tobacco use and low education is vital to decreasing the incidence of latestage presentations of lung cancer within these populations.     

Cause-specific and total mortality in the Canterbury (New Zealand) insulin-treated Diabetic Registry population: a 15-year follow-up study.

AIMS: To establish all-cause and cause-specific death rates, and risk factors for mortality in insulin-treated diabetic individuals living in the province of Canterbury, New Zealand. METHODS: Insulin-treated diabetic subjects (n = 995) on the Canterbury Diabetes Registry were followed up over 15 years and vital status determined. Death rates were standardized and hazard regression was used to model the effects of demographic covariates on relative survival time. RESULTS: There were 419 deaths in 11 226.3 person-years of follow-up with a standardized mortality ratio (SMR) of 2.0 (95% confidence interval (CI) 1.8-2.2). Relative mortality was greatest for the group aged 0-29 years (SMR 3.0 (95% CI 2.4-3.7)). After controlling for diabetes duration and gender, a 10-year increment in age of onset was associated with a 33% decrease in relative hazard (95% CI 29-36%), indicating that excess mortality due to diabetes declines with rising age of onset. After controlling for age of onset and gender, each 10-year increment in duration of diabetes is associated with a 26% decrease in relative hazard (95% CI 24-29%), indicating that with longer survival the mortality hazard approaches the general population hazard. Relative mortalities were increased for cardiovascular, renal and respiratory disease, but not malignancy. Relative mortality from acute metabolic complications was increased in the subgroup with age of onset of diabetes < 30 years and requiring insulin within 1 year of diagnosis. CONCLUSIONS: Mortality rates are high for insulin-treated diabetic individuals relative to the general population.     

Melatonin Lowers Plasma Prolactin Levels in Female Red Deer (Cervus elaphus)

The aim of the study was to determine the effect of exogenous melatonin treatment on circulating prolactin levels in red deer. Melatonin was administered from 12 June 1984 (day 1) to lactating and non-lactating hinds in the feed daily at 1600 h, and to non-lactating hinds by a subcutaneous implant. Average concentrations (ng/ml) of prolactin in plasma taken serially over 15-h periods were significantly higher for untreated hinds than for melatonin-treated animals on day 15 whether lactating (66-133 v. 23-28, P less than 0.05) or non-lactating (28-174 v. 8-13, P less than 0.01), remained higher on day 36 (lactating: 41-152 v. 15-21, P less than 0.05; non-lactating: 21-50 v. 1-7, P less than 0.001) but had decreased to similar levels on day 72 (lactating: 5-24 v. 7-17; non-lactating: 2-9 v. 0-4). The advanced reduction in plasma prolactin for all melatonin-treated hinds was associated with an advanced onset of seasonal breeding activity.     

Phenotype delineation of ZNF462 related syndrome

Zinc finger protein 462 (ZNF462) is a relatively newly discovered vertebrate specific protein with known critical roles in embryonic development in animal models. Two case reports and a case series study have described the phenotype of 10 individuals with ZNF462 loss of function variants. Herein, we present 14 new individuals with loss of function variants to the previous studies to delineate the syndrome of loss of function in ZNF462. Collectively, these 24 individuals present with recurring phenotypes that define a multiple congenital anomaly syndrome. Most have some form of developmental delay (79%) and a minority has autism spectrum disorder (33%). Characteristic facial features include ptosis (83%), down slanting palpebral fissures (58%), exaggerated Cupid's bow/wide philtrum (54%), and arched eyebrows (50%). Metopic ridging or craniosynostosis was found in a third of study participants and feeding problems in half. Other phenotype characteristics include dysgenesis of the corpus callosum in 25% of individuals, hypotonia in half, and structural heart defects in 21%. Using facial analysis technology, a computer algorithm applying deep learning was able to accurately differentiate individuals with ZNF462 loss of function variants from individuals with Noonan syndrome and healthy controls. In summary, we describe a multiple congenital anomaly syndrome associated with haploinsufficiency of ZNF462 that has distinct clinical characteristics and facial features.     

Nitric oxide detoxification systems enhance survival of Neisseria meningitidis in human macrophages and in nasopharyngeal mucosa

Nitric oxide (NO) contributes to mammalian host defense by direct microbicidal activity and as a signaling molecule of innate immune responses. Macrophages produce NO via the inducible NO synthase (iNOS). The genome of Neisseria meningitidis includes two genes, norB (encoding nitric oxide reductase) and cycP (encoding cytochrome c'), both of which detoxify NO in pure cultures of N. meningitidis. We show here that norB, and to a lesser extent cycP, enhance survival of N. meningitidis within primary human macrophages. Furthermore, accumulation of lysosome-associated membrane protein 1 (LAMP-1) is modified in phagosomes containing an isogenic norB mutant of N. meningitidis compared to the wild type. The survival enhancement conferred by norB and cycP is ablated by pretreatment of macrophages with the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA). Despite this evidence that NO detoxification confers advantage, we find, using a highly sensitive chemiluminescence technique, that human macrophage-associated [NO] is low even after activation by lipopolysaccharide and interferon alpha. Furthermore, wild-type N. meningitidis further depletes cell-associated NO during phagocytosis by an active mechanism and survives relatively poorly in the presence of L-NMMA, suggesting that the wild-type organism may utilize NO for optimal survival during intracellular life. The natural habitat of N. meningitidis is the human nasopharynx. Using a nasopharyngeal mucosa organ culture system, we show that mutants lacking norB and cycP also survive poorly in nasopharyngeal tissue compared to wild-type N. meningitidis. These findings indicate that the meningococcus requires active NO detoxification systems for optimal survival during experimental nasopharyngeal colonization and processing by human phagocytic cells.     

Polymorphonuclear leukocytes from patients with severe sepsis have lost the ability to degrade fibrin via u-PA

Fibrin persistence in the vasculature is an important complication of sepsis that can often lead to mortality. We have previously established that polymorphonuclear leukocytes (PMN) from healthy individuals have the capacity to degrade fibrin via urokinase-type plasminogen activator (u-PA). We have also demonstrated an increase in u-PA antigen in the plasma of patients suffering from septic shock. In this study, we investigate the hypothesis that PMN from patients with sepsis have lost their fibrinolytic ability and that this might contribute to the persistence of fibrin deposits. We show here that PMN from these patients do not express any u-PA activity, despite retaining some u-PA antigen. Additionally, thrombi prepared from the whole blood of the patients exhibit reduced endogenous lysis compared with those from healthy individuals. These data indicate that loss of fibrinolytic activity from PMN may be a contributing factor in fibrin persistence in the microvasculature in sepsis.     

A single institution experience with Laparoscopic Hernia repair in 791 children

IntroductionThere are many described technique to performing laparoscopic inguinal hernia repair in children. We describe our outcomes using a percutaneous internal ring suturing technique.MethodsA retrospective review of patients under 18 years old who underwent repair between January 2014 - March 2019 was performed. A percutaneous internal ring suturing technique, involving hydro-dissection of the peritoneum, percutaneous suture passage, and cauterization of the peritoneum in the sac prior to high ligation, was used. p < 0.05 was considered significant during the analysis.Results791 patients were included. The median age at operation was 1.9 years (IQR 0.37, 5.82). The median operative time for a unilateral repair was 21 min (IQR 16, 28), while the median time for a bilateral repair was 30.5 min (IQR 23, 41).In total, 3 patients required conversion to an open procedure (0.4%), 4 (0.6%) experienced post-operative bleeding, 9 (1.2%) developed a wound infection, and iatrogenic ascent of testis occurred in 10 (1.3%) patients. Twenty patients (2.5%) developed a recurrent hernia. All but two were re-repaired laparoscopically.ConclusionsThe use of percutaneous internal ring suturing for laparoscopic repair of inguinal hernias in the pediatric population is safe and effective with a low rate of complications and recurrence.     

"Prune Belly" syndrome.

A large sonolucent mass was first revealed by the ultrasonic echography examination of a fetus at 18 1/2 weeks' gestation, but was no longer present at 28 1/2 weeks' gestation. The fetus was subsequently born with the "prune belly" syndrome. The case is described, and the possible causes, and possibilities of prevention, of "prune belly" are discussed.